Solid-Phase Synthesis of Prenylcysteine Analogs

Prenylcysteine derivatives are of interest for a variety of different biological reasons, including probing the CaaX protein processing pathway. A solid-phase synthesis protocol for the preparation of prenylcysteines using 2-chlorotrityl chloride resin as a solid support has been developed. A series...

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Bibliographic Details
Published in:Journal of organic chemistry 2009-04, Vol.74 (8), p.2975-2981
Main Authors: Donelson, James L, Hodges-Loaiza, Heather B, Henriksen, Brian S, Hrycyna, Christine A, Gibbs, Richard A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Analytical, structural and metabolic biochemistry
Biological and medical sciences
Chromatography, High Pressure Liquid
Cysteine - analogs & derivatives
Cysteine - chemical synthesis
Cysteine - chemistry
Enzymes and enzyme inhibitors
Fundamental and applied biological sciences. Psychology
Humans
Molecular Structure
Protein Methyltransferases - chemistry
Protein Methyltransferases - metabolism
Solid Phase Extraction
Transferases
Trityl Compounds - chemistry
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Summary:Prenylcysteine derivatives are of interest for a variety of different biological reasons, including probing the CaaX protein processing pathway. A solid-phase synthesis protocol for the preparation of prenylcysteines using 2-chlorotrityl chloride resin as a solid support has been developed. A series of novel amide-modified farnesylcysteine analogs were synthesized in both high purity and yield under mild conditions. The farnesylcysteine analogs were evaluated using human isoprenylcysteine carboxyl methyltransferase as a biological target, and several new inhibitors, one with significantly enhanced potency, were identified.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo8021692